Glycolysis/gluconeogenesis- and tricarboxylic acid cycle–related metabolites, Mediterranean diet, and type 2 diabetes. Issue 4 (14th February 2020)

• Record Type: Journal Article
• Authors: Guasch-Ferré, Marta; Santos, José L; Martínez-González, Miguel A; Clish, Clary B; Razquin, Cristina; Wang, Dong; Liang, Liming; Li, Jun; Dennis, Courtney; Corella, Dolores; Muñoz-Bravo, Carlos; Romaguera, Dora; Estruch, Ramón; Santos-Lozano, José Manuel; Castañer, Olga; Alonso-Gómez, Angel; Serra-Majem, Luis; Ros, Emilio; Canudas, Sílvia; Asensio, Eva M; Fitó, Montserrat; Pierce, Kerry; Martínez, J Alfredo; Salas-Salvadó, Jordi; Toledo, Estefanía; Hu, Frank B; Ruiz-Canela, Miguel
• Is Part Of: American journal of clinical nutrition. Volume 111:Issue 4(2020)
• Page Start: 835
• Page End: 844
• Publication Date: 2020-02-14
• Subjects: glycolysis metabolites -- tricarboxylic acid cycle metabolites -- metabolomics -- type 2 diabetes -- insulin resistance; Diet therapy -- Periodicals; Nutrition -- Periodicals; Dietetics -- Periodicals; 613.205
• DOI: 10.1093/ajcn/nqaa016
• Languages: English
• ISSNs: 0002-9165

Abstract

ABSTRACT: Background: Glycolysis/gluconeogenesis and tricarboxylic acid (TCA) cycle metabolites have been associated with type 2 diabetes (T2D). However, the associations of these metabolites with T2D incidence and the potential effect of dietary interventions remain unclear. Objectives: We aimed to evaluate the association of baseline and 1-y changes in glycolysis/gluconeogenesis and TCA cycle metabolites with insulin resistance and T2D incidence, and the potential modifying effect of Mediterranean diet (MedDiet) interventions. Methods: We included 251 incident T2D cases and 638 noncases in a nested case-cohort study within the PREDIMED Study during median follow-up of 3.8 y. Participants were allocated to MedDiet + extra-virgin olive oil, MedDiet + nuts, or control diet. Plasma metabolites were measured using a targeted approach by LC–tandem MS. We tested the associations of baseline and 1-y changes in glycolysis/gluconeogenesis and TCA cycle metabolites with subsequent T2D risk using weighted Cox regression models and adjusting for potential confounders. We designed a weighted score combining all these metabolites and applying the leave-one-out cross-validation approach. Results: Baseline circulating concentrations of hexose monophosphate, pyruvate, lactate, alanine, glycerol-3 phosphate, and isocitrate were significantly associated with higher T2D risk (17–44% higher risk for each 1-SD increment). The weighted score including all metabolites was associated with a 30% (95% CI: 1.12, 1.51) higher relative risk of T2D for each 1-SD increment. Baseline lactate and alanine were associated with baseline and 1-y changes of homeostasis model assessment of insulin resistance. One-year increases in most metabolites and in the weighted score were associated with higher relative risk of T2D after 1 y of follow-up. Lower risks were observed in the MedDiet groups than in the control group although no significant interactions were found after adjusting for multiple comparisons. Conclusions: We identified a panel of glycolysis/gluconeogenesis-related metabolites that was significantly associated with T2D risk in a Mediterranean population at high cardiovascular disease risk. A MedDiet could counteract the detrimental effects of these metabolites. This trial was registered at controlled-trials.com as ISRCTN35739639.